The goals of this project are to understand how spinal circuits are used to coordinate normal movement in humans and how malfunctioning of spinal circuits contributes to abnormal movements in neurological disorders. We have particularly focused on disorders of voluntary movement with excessive muscle contraction, such as Stiffperson syndrome and spasticity. During FY2001, most of our efforts focused on defining clinical subtypes of primary lateral sclerosis, a degenerative disorder of corticospinal neurons that produces profound spasticity and slowness of movement. In a subset of these patients physiological measures showed that only the corticospinal tract is involved, while primitive motor pathways are preserved. The motor cortex is inexcitable relatively early in the course of the disease, when strength and muscle bulk are preserved. In contrast to amyotrophic lateral sclerosis, early hyperexcitability was not seen. The long term effects of corticospinal dysfunction on spinal excitability and motor neuron function are presently being assessed.